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The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10−20), thalamus (p = 7.46 × 10−10), caudate (p = 1.97 × 10−18), putamen (p = 1.7 × 10−12), and nucleus accumbens (p = 1.99 × 10−7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = −0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p −19) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10−7) or PTSD (rs10861272; p = 1.78 × 10−6) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.

Background Atypical auditory processing (AAP) in psychotic psychopathology is evident in early (N1), mid-latency (P2/N2/mismatch negativity), and late (P3) neural responses. The influence of attention on AAP, and how temporal stages of AAP are associated with phenomenology of psychotic psychopathology are not well understood. Methods We used a directed attention oddball task to characterize stages of AAP in psychosis and to examine the influence of selective attention. Ninety patients with schizophrenia (SCZ), 53 patients with bipolar disorder (BP), 90 healthy controls and 72 first-degree relatives of SCZ (SREL) were studied. We used principal components analysis to decompose average-reference 64-channel subject-level ERPs. Results Altered attentional modulation was evident in SCZ at early (N1 factor) and late (P3 factor) stages of AAP, but not at mid-latency P2 factor. Irrespective of condition, N1 and P3 were reduced in SCZ, which predicted greater psychopathology and schizotypal personality traits. Diminished mid-latency mismatch detection (P2 factor) was evident in SCZ, BP, and SREL and was associated with greater positive symptoms of psychosis as well as self-reported atypical cognitive-perceptual experiences. Conclusions Attentional modulation of early N1, and later P3 neural responses was atypical in patients, but the degree of attentional modulation did not relate to symptom severity or schizotypal traits. Our findings suggest the link between mid-latency mismatch detection and atypical cognitive/perceptual experiences is not driven by attentional deficits alone and point to the promise of mid-latency mismatch detection as a candidate endophenotype and intervention target.

Among individuals with posttraumatic stress disorder (PTSD), verbal learning and memory are areas of weakness compared with other cognitive domains (e.g., visuospatial memory). In this study, previously deployed military veterans completed clinical assessments of word memory and vocabulary ( n = 243) and a laboratory task measuring encoding, free recall, repetition priming, and recognition of words ( n = 147). Impaired verbal memory was selectively related to reexperiencing symptoms of PTSD but was not associated with other symptom groupings or blast-induced traumatic brain injury. Implicit priming of response times following word repetition was also unrelated to clinical symptoms. Instead, slowed response times during encoding explained associations between reexperiencing and memory performance. These findings are consistent with alterations in attentional control explaining PTSD-related verbal-memory deficits. Such findings have implications for understanding trauma-focused psychotherapy and recovery, which may depend on efficient attentional processing of words to alter posttraumatic reexperiencing symptoms.

Psychological resilience as a longitudinal process is highly relevant for understanding the functioning outcomes of military populations. Here, we review the extant literature on resilience among military service members, focusing on National Guard Soldiers. Our specific project (Advancing Research on Mechanisms of Resilience, “ARMOR”) aims to develop a comprehensive model of resilience using a multilevel perspective. We report results from our prospective pilot study (n = 103) conducted in preparation for our large-scale longitudinal cohort study of Basic Combat Training (BCT) and its impact on military recruits’ wellbeing. Results support feasibility of the larger study, evidence for a new measure of BCT stressor exposure, and demonstrate preliminary associations with BCT-related stressors and longitudinal changes in adaptive functioning. Future directions for our larger study will utilize data from survey responses, structured clinical interviews, neurobehavioral tasks, and neurobiological measures (functional and structural MRI and electroencephalography [EEG]) to examine individual differences in self-regulation as a predictor of resilience-related processes. ARMOR is well positioned to elucidate mechanisms that could be targeted for promoting wellbeing, preventing psychopathology, and facilitating long-term recovery.

Psychotic disorders have been associated with visual deficits and deviant semantic processing, making it unclear whether object detection abnormalities in psychosis originate from low-level or higher-order visual processes. The current study investigated how high-level visual processing is affected in psychosis by presenting object stimuli with equivalent low-level visual features. Outpatients with affective and nonaffective psychotic disorders, first-degree biological relatives, and psychiatrically unaffected individuals (N = 130) completed the Fragmented Ambiguous Object Task (FAOT) to assess recognition of objects in ambiguous stimuli. During the task, we recorded electroencephalography, quantified event-related potential (ERP) components (P1, N1, negative closure [NCL], N400), and derived four spatiotemporal event-related potential factors using principal components analysis (PCA). In addition to traditional diagnoses, psychosis was characterized using a dimensional measure of individual differences in self-reported sensory experiences (perceptual absorption) calculated from scales that tap the psychotic domain of the hierarchical structure of psychopathology. Rates of detecting objects within fragmented stimuli failed to differ across diagnostic groups or significantly predict perceptual absorption (p = .057). PCA factors that reflected smaller N1 and larger NCL amplitudes were associated with detecting objects. Exploratory analyses revealed that higher perceptual absorption was associated with reductions in the N400 and a late positive PCA factor. Although early and midlatency brain responses modulate during object detection, late brain responses tied to semantic appraisal of objects are related to perceptual aberrations often reported by individuals with severe psychopathology. Dimensional measures of personality appear sensitive to variation in biological systems relevant to psychotic symptomatology and object perception. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Investigations within the Human Connectome Project have expanded to include studies focusing on brain disorders. This paper describes one of the investigations focused on psychotic psychopathology: The psychosis Human Connectome Project (P-HCP). The data collected as part of this project were multimodal and derived from clinical assessments of psychopathology, cognitive assessments, instrument-based motor assessments, blood specimens, and magnetic resonance imaging (MRI) data. The dataset will be made publicly available through the NIMH Data Archive. In this report we provide specific information on how the sample of participants was obtained and characterized and describe the experimental tasks and procedures used to probe neural functions involved in psychotic disorders that may also mark genetic liability for psychotic psychopathology. Our goal in this paper is to outline the data acquisition process so that researchers intending to use these publicly available data can plan their analyses. MRI data described in this paper are limited to data acquired at 3 Tesla. A companion paper describes the study's 7 Tesla image acquisition protocol in detail, which is focused on visual perceptual functions in psychotic psychopathology.

The brain at rest generates cycles of electrical activity that have been shown to be abnormal in people with schizophrenia. The alpha rhythm (~ 10 Hz) is the dominant resting state electrical cycle and each person has a propensity toward a particular frequency of oscillation for this rhythm. This individual alpha peak frequency (IAPF) is hypothesized to be central to visual perceptual processes and may have downstream influences on cognitive functions such as attention, working memory, or problem solving. In the current study we sought to determine whether IAPF was slower in schizophrenia, and whether lower IAPF predicted deficits in visual perception and cognition that are often observed in schizophrenia. Eyes-closed resting state EEG activity, visual attention, and global cognitive functioning were assessed in individuals with schizophrenia (N = 104) and a group of healthy controls (N = 101). Compared to controls, the schizophrenia group showed slower IAPF and was associated with poorer discrimination of visual targets and nontargets on a computerized attention task, as well as impaired global cognition measured using neuropsychological tests across groups. Notably, disruptions in visual attention fully mediated the relationship between IAPF and global cognition across groups. The current findings demonstrate that slower alpha oscillatory cycling accounts for global cognitive deficits in schizophrenia by way of impairments in perceptual discrimination measured during a visual attention task.

Posttraumatic stress disorder (PTSD) is marked by alterations in emotional functioning, physiological reactivity, and attention. Neural reactivity to acoustic startle stimuli can be used to understand brain functions related to these alterations. Investigations of startle reactivity in PTSD have yielded inconsistent findings, which may reflect the heterogeneity of the disorder. Furthermore, little is known of how the common co-occurrence of mild traumatic brain injury (mTBI; i.e., concussion) may influence neural reactivity. We examined the event-related potentials (ERPs) of combat veterans (n = 102) to acoustic startle probes delivered during viewing of pleasant, neutral, unpleasant, and combat-related pictures. Interview-based assessments yielded dimensional characterizations of PTSD and mTBI. The P3 ERP response to startle probes was reduced during all affective relative to neutral pictures but failed to be associated with a PTSD diagnosis. However, two separable domains of PTSD symptomatology were associated with startle ERPs regardless of the picture conditions. Maladaptive avoidance was associated with smaller N1, P2, and P3 amplitudes, while intrusive reexperiencing was associated with larger P2 amplitudes. There were no main effects of mTBI. Findings suggest that level of symptomatology rather than a formal diagnosis of PTSD better explains alterations in neural reactivity after traumatic events, while mild brain injuries have little impact. Avoidance symptoms of PTSD may dampen neural functions that facilitate reorientation to threat while intrusive reexperiencing of traumatic events appears to heighten sensory reactivity. Considering specific aspects of symptomatology provides insight into the neural basis of trauma-related psychopathology and may help guide individualization of clinical interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The brain at rest generates cycles of electrical activity that have been shown to be abnormal in people with schizophrenia. The alpha rhythm (~ 10 Hz) is the dominant resting state electrical cycle and each person has a propensity toward a particular frequency of oscillation for this rhythm. This individual alpha peak frequency (IAPF) is hypothesized to be central to visual perceptual processes and may have downstream influences on cognitive functions such as attention, working memory, or problem solving. In the current study we sought to determine whether IAPF was slower in schizophrenia, and whether lower IAPF predicted deficits in visual perception and cognition that are often observed in schizophrenia. Eyes-closed resting state EEG activity, visual attention, and global cognitive functioning were assessed in individuals with schizophrenia (N = 104) and a group of healthy controls (N = 101). Compared to controls, the schizophrenia group showed slower IAPF and was associated with poorer discrimination of visual targets and nontargets on a computerized attention task, as well as impaired global cognition measured using neuropsychological tests across groups. Notably, disruptions in visual attention fully mediated the relationship between IAPF and global cognition across groups. The current findings demonstrate that slower alpha oscillatory cycling accounts for global cognitive deficits in schizophrenia by way of impairments in perceptual discrimination measured during a visual attention task.

The Sensory Gating Inventory (SGI) is a 36-item measure used to assess an individual’s subjective ability to modulate, filter, over-include, discriminate, attend to, and tolerate sensory stimuli. Due to its theoretical and empirical link with sensory processing deficits, this measure has been used extensively in studies of psychosis and other psychopathology. The current work fills a need within the field for a briefer measure of sensory gating aberrations that maintains the original measure’s utility. For this purpose, large samples (total n = 1552) were recruited from 2 independent sites for item reduction/selection and brief measure validation, respectively. These samples reflected subgroups of individuals with a psychosis-spectrum disorder, at high risk for a psychosis-spectrum disorder, nonpsychiatric controls, and nonpsychosis psychiatric controls. Factor analyses and item-response models were used to create the SGI-Brief (SGI-B; 10 Likert-rated items), a unidimensional self-report measure that retains the original SGI’s transdiagnostic (ie, present across disorders) utility and content breadth. Findings show that the SGI-B has excellent psychometric properties (alpha = 0.92) and demonstrates external validity through strong associations with measures of psychotic symptomatology, theoretically linked measures of personality (eg, perceptual dysregulation), and modest associations with laboratory-based sensory processing tasks in the auditory and visual domains on par with the original version. Accordingly, the SGI-B will be a valuable tool for dimensional and transdiagnostic examination of sensory gating abnormalities within clinical science research, while reducing administrator and participant burden.

Background People with schizophrenia (PSZ) have profound deficits in context processing, an executive process that guides adaptive behaviors according to goals and stored contextual information. Although various neural processes are involved in context processing and are affected in PSZ, the core underlying neural dysfunction is unclear. Methods To determine the relative importance of neural dysfunctions within prefrontal cognitive control, sensory activity, and motor activity to context processing deficits in PSZ, we examined event-related potentials (ERPs) in 60 PSZ and 51 healthy control subjects during an optimal context processing task. We also analyzed the Ex-Gaussian reaction time distribution to examine abnormalities in motor control variability in PSZ. Results Compared with healthy control subjects, PSZ had lower response accuracy and greater variability in their normal reaction times during high context processing demands. Latencies of normal and slow responses were generally increased in PSZ. High context processing–related reductions in frontal ERPs were indicative of specific deficits in proactive and reactive cognitive controls in PSZ, while ERPs associated with visual and motor processes were reduced regardless of context processing demands, indicating generalized visuomotor deficits. In contrast to previous studies, we found that diminished frontal responses reflective of proactive control of the contextual cue, rather than visual responses of cue encoding, predicted response accuracy deficits in PSZ. In addition, probe-related ERP components of motor preparation, prefrontal reactive control, and frontomotor interaction predicted Ex-Gaussian indices of reaction time instability in PSZ. Conclusions Prefrontal proactive and reactive control deficits associated with failures in using mental representation likely underlie context processing deficits in PSZ.

Hypersensitivity to reward-relevant stimuli is theorized to be a core etiological factor in bipolar disorders (BD). However, little is known about the role of cognitive control dysregulation within reward contexts in BD, particularly during adolescence. Using electroencephalography (EEG), we explored alterations in cognitive control processes and approach motivation in 99 adolescents with (n=53) and without (n=46) BD during reward striving (target anticipation) and reward attainment (feedback) phases of a monetary incentive delay (MID) task. Time-frequency analysis yielded frontal theta and frontal alpha asymmetry as indices of cognitive control and approach motivation, respectively. Multilevel mixed models examined group differences, as well as age, sex and other effects, on frontal theta and frontal alpha asymmetry during both phases of the task and on performance accuracy and reaction times. Healthy adolescent girls exhibited lower frontal theta than both adolescent girls with BD and also adolescent boys with and without BD during reward anticipation and feedback. Across groups, adolescent boys displayed greater relative left frontal alpha activity than adolescent girls during reward anticipation and feedback. Behaviorally, adolescents with BD exhibited faster responses on both positively- and negatively-motivated trials versus neutral trials, whereas healthy adolescents had faster responses only on positively-motivated trials; adolescents with BD were less accurate in responding to neutral trials compared to healthy controls. These findings shed light on normative and BD-specific involvement of approach motivation and cognitive control during different stages of reward processing in adolescence and, further, provide evidence of adolescent sex differences in these processes.

Posttraumatic stress disorder (PTSD) is a complex psychiatric condition that has generated much attention in the neuroimaging literature. A neurocircuitry model supporting fronto-limbic dysfunction as a major player in facilitating clinical symptoms of PTSD is well-characterized; however, recent literature suggests that network-based approaches may provide additional insight into neural dysfunction in PTSD. Our analysis uses resting-state neuroimaging scans of 1063 adults from the PGC-ENIGMA PTSD Consortium to investigate a network-based model of functional connectivity in PTSD. With a novel, resolution limit-free community detection approach, 16 communities corresponding to functionally meaningful networks were detected with high quality. After group-level community detection, participants were classified into three groups (PTSD, n=418, trauma-exposed controls without PTSD, n=434, and non-trauma exposed healthy controls, n=211). Individual network connectivity metrics were calculated, including whole-brain, default mode network, and central executive network participation coefficient and connectivity strength. Linear mixed effects models revealed group differences in the whole-brain, default mode, and central executive network participation coefficient and connectivity strength such that individuals with PTSD demonstrated overall greater values. We also described sex differences such that males demonstrate greater whole-brain participation coefficient vs. females and females demonstrate greater default mode network connectivity strength vs. males. Our results suggest that PTSD in adults is associated with reduced specialization and enhanced inter-module communication throughout the brain network, which may contribute to inefficient information processing and poor emotional regulation. This study presents a novel use of resolution limit-free community detection in a large PTSD sample, revealing robust differences in resting-state network topology.

IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subjects’ data from 29 cohorts in five countries (n=3439).MethodsUsing Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN.ResultsNotable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comorbid PTSD and MDD showed higher CT-based centrality in the right anterior cingulate gyrus, right parahippocampal gyrus and lower SA-based centrality in left insular gyrus.ConclusionUnlike previous studies with smaller sample sizes (≤318), our study found differences in centrality measures using a sample size of 3439 subjects. This is the first cross-sectional study to examine SCN interactions with age, sex, and comorbid MDD. Although limited to group level inferences, centrality measures offer insights into a node’s relationship to the entire functional connectome unlike approaches like seed-based connectivity or independent component analysis. Nodes having higher centrality have greater structural or functional connections, lending them invaluable for translational treatments like neuromodulation.

Background Dysfunctional connectivity within the perceptual hierarchy is proposed to be an integral component of psychosis. The fragmented ambiguous object task was implemented to investigate neural connectivity during object recognition in patients with schizophrenia (SCZ) and bipolar disorder and first-degree relatives of patients with SCZ (SREL). Methods We analyzed 3T functional magnetic resonance imaging data collected from 27 patients with SCZ, 23 patients with bipolar disorder, 24 control subjects, and 19 SREL during the administration of the fragmented ambiguous object task. Fragmented ambiguous object task stimuli were line-segmented versions of objects and matched across a number of low-level features. Images were categorized as meaningful or meaningless based on ratings assigned by the participants. Results An a priori region of interest was defined in the primary visual cortex (V1). In addition, the lateral occipital complex/ventral visual areas, intraparietal sulcus (IPS), and middle frontal gyrus (MFG) were identified functionally via the contrast of cortical responses to stimuli judged as meaningful or meaningless. SCZ was associated with altered neural activations at V1, IPS, and MFG. Psychophysiological interaction analyses revealed negative connectivity between V1 and MFG in patient groups and altered modulation of connectivity between conditions from right IPS to left IPS and right IPS to left MFG in patients with SCZ and SREL. Conclusions Results provide evidence that SCZ is associated with inefficient processing of ambiguous visual objects at V1, which is likely attributable to altered feedback from higher-level visual areas. We also observed distinct patterns of aberrant connectivity among low-level, mid-level, and high-level visual areas in patients with SCZ, patients with bipolar disorder, and SREL.

BackgroundGeneralization of conditioned-fear, a core feature of post-traumatic stress disorder (PTSD), has been the focus of several recent neuroimaging studies. A striking outcome of these studies is the frequency with which neural correlates of generalization fall within hubs of well-established functional networks including salience (SN), central executive (CEN), and default networks (DN). Neural substrates of generalization found to date may thus reflect traces of large-scale brain networks that form more expansive neural representations of generalization. The present study includes the first network-based analysis of generalization and PTSD-related abnormalities therein.MethodsfMRI responses in established intrinsic connectivity networks (ICNs) representing SN, CEN, and DN were assessed during a generalized conditioned-fear task in male combat veterans (N = 58) with wide-ranging PTSD symptom severity. The task included five rings of graded size. Extreme sizes served as conditioned danger-cues (CS+: paired with shock) and safety-cues (CS−), and the three intermediate sizes served as generalization stimuli (GSs) forming a continuum-of-size between CS+ and CS–. Generalization-gradients were assessed as behavioral and ICN response slopes from CS+, through GSs, to CS–. Increasing PTSD symptomatology was predicted to relate to less-steep slopes indicative of stronger generalization.ResultsSN, CEN, and DN responses fell along generalization-gradients with levels of generalization within and between SN and CEN scaling with PTSD symptom severity.ConclusionsNeural substrates of generalized conditioned-fear include large-scale networks that adhere to the functional organization of the brain. Current findings implicate levels of generalization in SN and CEN as promising neural markers of PTSD.

Approximately 275,000 American service members deployed to Iraq or Afghanistan have sustained a mild traumatic brain injury (mTBI), with 75% of these incidents involving an explosive blast. Combat-related mTBI is frequently associated with comorbid mental health disorders, especially posttraumatic stress disorder (PTSD). Attention problems, including sustained attention, are common cognitive complaints of veterans with TBI and PTSD. The present study sought to examine neural correlates of sustained attention in veterans with blast mTBI and/or current PTSD. In 124 veterans of Operations Enduring and Iraqi Freedom (OEF/OIF), we examined event-related potentials (ERPs) elicited by targets and non-targets during performance of a degraded-stimulus continuous performance task (DS-CPT). Four groups, consisting of veterans with blast-related mTBI only, current PTSD only, both blast mTBI and PTSD, and a control group, were studied. Compared to all other groups, blast mTBI only participants were more likely to respond regardless of stimulus type during the DS-CPT. During target detection, the three mTBI/PTSD groups showed reduced amplitude of the P3b (i.e., P300) ERP at Pz compared to the control group. P3b of the three affected groups did not differ from each other. These results suggest that parietal P3b amplitude reduction during target detection in the DS-CPT task may be an index of brain pathology after combat trauma, yet the diminished brain response fails to differentiate independent effects of blast-related mTBI or severity of PTSD symptomatology.

Objective To better understand the origins of working memory (WM) impairment in schizophrenia we investigated cortical oscillatory activity in people with schizophrenia (PSZ) while they performed a WM task requiring encoding, maintenance, and retrieval/manipulation processes of spatial information. Methods We examined time–frequency synchronous energy of cortical source signals that were derived from magnetoencephalography (MEG) localized to cortical regions using WM−related hemodynamic responses and individualized structural head-models. Results Compared to thirteen healthy controls (HC), twelve PSZ showed performance deficits regardless of WM−load or duration. During encoding, PSZ had early theta and delta event-related synchrony (ERS) deficits in prefrontal and visual cortices which worsened with greater memory load and predicted WM performance. During prolonged maintenance of material, PSZ showed deficient beta event-related desynchrony (ERD) in dorsolateral prefrontal, posterior parietal, and visual cortices. In retrieval, PSZ showed reduced delta/theta ERS in the anterior prefrontal and ventral visual cortices and diminished gamma ERS in the premotor and posterior parietal cortices. Conclusions Although beta/gamma cortical neural oscillatory deficits for maintenance/retrieval are evident during WM, the abnormal prefrontal theta-frequency ERS for encoding is most predictive of poor WM in schizophrenia. Significance Time-frequency-spatial analysis identified process- and frequency-specific neural synchrony abnormalities underlying WM deficits in schizophrenia.

Identifying the pathophysiology of posttraumatic stress disorder (PTSD) is a critical step toward reducing its debilitating impact. Spontaneous neural activity, measured at rest using various neuroimaging techniques (e.g., regional homogeneity [ReHo], amplitude of low frequency fluctuations [ALFF]), can provide insight about baseline neurobiological factors influencing sensory, cognitive, or behavioral processes associated with PTSD. The present study used activation likelihood estimation (ALE) to conduct the largest‐to‐date quantitative meta‐analysis of spontaneous neural activity in PTSD, including 457 PTSD cases, 292 trauma‐exposed controls (TECs), and 293 non‐traumatized controls (NTCs) across 22 published studies. Five regions‐of‐interest (ROIs) were identified where activity differed between PTSD cases and controls: one when compared to all controls (left globus pallidus), two when compared to TECs (left inferior parietal lobule [IPL] and right lingual gyrus), and two when compared to NTCs (left amygdala and right caudate head). To corroborate these results, a second analysis was conducted using resting‐state functional magnetic resonance imaging on an independent sample of 205 previously‐deployed US military veterans. In this analysis, converging evidence from ReHo and ALFF showed that spontaneous neural activity in the left IPL alone was positively correlated with PTSD symptom severity. This result is consistent with theoretical accounts that link left IPL activity with PTSD‐relevant processes such as processing of emotional stimuli (e.g., fearful faces) and the extent that attention is captured by salient autobiographical memories. By modeling the neurobiological correlates of PTSD, we can increase our understanding of this debilitating disorder and guide the development of future clinical innovations.

OBJECTIVE: Special attention has been given to verbal memory deficits in schizophrenia because they are apparent in healthy biological relatives of affected individuals, indicating a link to genetic risk for the disorder. Despite a growing consensus that encoding abnormalities contribute to poor verbal memory in the disorder, few studies have directly examined how neural responses during encoding contribute to later memory performance. METHOD: We evaluated event-related potentials (ERPs) during encoding of verbal material by patients with schizophrenia, healthy first-degree biological relatives of patients, and healthy controls. The extent to which N1, N400, and anterior and parietal Late Positive Components (LPCs) explained encoding accuracy and later memory of material was investigated. RESULTS: Encoding accuracy was associated with asymmetry in anterior LPCs toward right frontal brain regions and was most evident in relatives. N1 was abnormal at encoding in schizophrenia and differentially accounted for later memory performance. In controls better recall of verbal material was predicted by a larger early occipital (N1) encoding response; however, in patients with schizophrenia smaller N1 encoding responses were related to better recall. Interestingly, better recognition of verbal material across groups was also predicted by smaller N1 amplitudes during encoding of word stimuli. CONCLUSION: Separable patterns of electrophysiological response during encoding appear to differentially support recall and recognition of material from memory. Similar patterns of electrophysiological response across patient and relative groups suggest that those who carry genetic liability for schizophrenia share deviations in the neural activity related to encoding of material into episodic memory.

Posttraumatic stress disorder (PTSD) and sequelae of mild traumatic brain injury (mTBI) are presumed to contribute to reintegration difficulties in combat-exposed veterans. Yet their relative impacts on postdeployment functioning are not well understood. The current study used structural equation modeling (SEM) to clarify the extent to which symptoms of internalizing disorders (e.g., depression, anxiety), mTBI symptoms, and cognitive performance are associated with functional impairment in 295 combat-exposed veterans. SEM results showed that internalizing symptoms most significantly predicted functional impairment ( r = 0.72). Blast mTBI and cognitive performance were associated with internalizing ( r = 0.24 and −0.25, respectively), but functional impairment was only modestly related to cognition ( r = −0.17) and unrelated to mTBI. These results indicate that internalizing symptoms are the strongest predictor of functioning in trauma-exposed veterans, exceeding the effects of mTBI and cognitive performance. This evidence supports prioritizing interventions that target internalizing psychopathology to improve functioning in cases of co-occurring PTSD and mTBI.

OBJECTIVE: Heightened generalization of fear from an aversively reinforced conditioned stimulus (CS+, a conditioned danger cue) to resembling stimuli is widely accepted as a pathogenic marker of posttraumatic stress disorder (PTSD). Indeed, a distress response to benign stimuli that “resemble” aspects of the trauma is a central feature of the disorder. To date, the link between overgeneralization of conditioned fear and PTSD derives largely from clinical observations, with limited empirical work on the subject. This represents the first effort to examine behavioral and brain indices of generalized conditioned fear in PTSD using systematic methods developed in animals known as generalization gradients: the gradual decline in conditioned responding as the presented stimulus gradually differentiates from CS+. METHOD: Gradients of conditioned fear generalization were assessed using functional MRI and behavioral measures in U.S. combat veterans who served in Iraq or Afghanistan and had PTSD (N=26), subthreshold PTSD (N=19), or no PTSD (referred to as trauma control subjects) (N=17). Presented stimuli included rings of graded size, with extreme sizes serving as CS+ (paired with shock) and as a nonreinforced conditioned stimulus (CS−, a conditioned safety cue), and with intermediate sizes forming a continuum of similarity between CS+ and CS−. Generalization gradients were assessed as response slopes from CS+, through intermediate ring sizes, to CS−, with less steep slopes indicative of stronger generalization. RESULTS: Relative to trauma control subjects, PTSD patients showed stronger conditioned generalization, as evidenced by less steep generalization gradients in both behavioral risk ratings and brain responses in the left and right anterior insula, left ventral hippocampus, dorsolateral and dorsomedial prefrontal cortex, and caudate nucleus. Severity of PTSD symptoms across the three study groups was positively correlated with levels of generalization at two such loci: the right anterior insula and left ventral hippocampus. CONCLUSIONS: The results point to evidence of brain-based markers of overgeneralized fear conditioning related to PTSD. These findings provide further understanding of a central yet understudied symptom of trauma-related psychopathology.

Psychosis has been associated with neural anomalies across a number of brain regions and cortical networks. Nevertheless, the exact pathophysiology of the disorder remains unclear. Aberrant visual perceptions such as hallucinations are evident in psychosis, while the occurrence of visual distortions is elevated in individuals with genetic liability for psychosis. The overall goals of this project are to: (1) use psychophysical tasks and neuroimaging to characterize deficits in visual perception; (2) acquire a mechanistic understanding of these deficits through development and validation of a computational model; and (3) determine if said mechanisms mark genetic liability for psychosis. Visual tasks tapping both low- and high-level visual processing are being completed as individuals with psychotic disorders (IPD), first-degree biological siblings of IPDs (SibIPDs) and healthy controls (HCs) undergo 248-channel magneto-encephalography (MEG) recordings followed by 7 Tesla functional magnetic resonance imaging (MRI). By deriving cortical source signals from MEG and MRI data, we will characterize the timing, location and coordination of neural processes. We hypothesize that IPDs prone to visual hallucinations will exhibit deviant functions within early visual cortex, and that aberrant contextual influences on visual perception will involve higher-level visual cortical regions and be associated with visual hallucinations. SibIPDs who experience visual distortions—but not hallucinations—are hypothesized to exhibit deficits in higher-order visual processing reflected in abnormal inter-regional neural synchronization. We hope the results lead to the development of targeted interventions for psychotic disorders, as well as identify useful biomarkers for aberrant neural functions that give rise to psychosis.

Sensory discrimination thresholds (i.e., the briefest stimulus that can be accurately perceived) can be measured using tablet-based auditory and visual sweep paradigms. These basic sensory functions have been found to be diminished in patients with psychosis. However, the extent to which worse sensory discrimination characterizes genetic liability for psychosis, and whether it is related to clinical symptomatology and community functioning remains unknown. In the current study we compared patients with psychosis (PSY; N=76), their first-degree biological relatives (REL; N=44), and groups of healthy controls (CON; N=13 auditory and visual/N=275 auditory/N=267 visual) on measures of auditory and visual sensory discrimination, and examined relationships with a battery of symptom, cognitive, and functioning measures. Sound sweep thresholds differed among the PSY, REL, and CON groups, driven by higher thresholds in the PSY compared to CON group, with the REL group showing intermediate thresholds. Visual thresholds also differed among the three groups, driven by higher thresholds in the REL versus CON group, and no significant differences between the REL and PSY groups. Across groups and among patients, higher thresholds (poorer discrimination) for both sound and visual sweeps strongly correlated with lower global cognitive scores. We conclude that low-level auditory and visual sensory discrimination deficits in psychosis may reflect genetic liability for psychotic illness. Critically, these deficits relate to global cognitive disruptions that are a hallmark of psychotic illnesses such as schizophrenia.

BackgroundAccurate perception of visual contours is essential for seeing and differentiating objects in the environment. Both the ability to detect visual contours and the influence of perceptual context created by surrounding stimuli are diminished in people with schizophrenia (SCZ). The central aim of the present study was to better understand the biological underpinnings of impaired contour integration and weakened effects of perceptual context. Additionally, we sought to determine whether visual perceptual abnormalities reflect genetic factors in SCZ and are present in other severe mental disorders.MethodsWe examined behavioral data and event-related potentials (ERPs) collected during the perception of simple linear contours embedded in similar background stimuli in 27 patients with SCZ, 23 patients with bipolar disorder (BP), 23 first-degree relatives of SCZ, and 37 controls.ResultsSCZ exhibited impaired visual contour detection while BP exhibited intermediate performance. The orientation of neighboring stimuli (i.e. flankers) relative to the contour modulated perception across all groups, but SCZ exhibited weakened suppression by the perceptual context created by flankers. Late visual (occipital P2) and cognitive (centroparietal P3) neural responses showed group differences and flanker orientation effects, unlike earlier ERPs (occipital P1 and N1). Moreover, behavioral effects of flanker context on contour perception were correlated with modulation in P2 & P3 amplitudes.ConclusionIn addition to replicating and extending findings of abnormal contour integration and visual context modulation in SCZ, we provide novel evidence that the abnormal use of perceptual context is associated with higher-order sensory and cognitive processes.

Objectives Many combat veterans exhibit cognitive limitations of uncertain origin. In this study, we examined factors that predict cognitive functioning by considering effects of blast-related concussion (BRC), non-blast-related concussion (NBRC), and posttraumatic stress disorder (PTSD) symptoms. Analyses specifically tested whether (a) BRC and NBRC were distinct in their prediction of cognitive performance; (b) a dose-response relationship existed between recurrent concussion (BRC and NBRC) and cognitive impairment; and (c) PTSD symptoms mediated the relationship between BRC and cognitive performance. Method Two hundred eighty veterans with combat zone deployment histories completed semistructured clinical interviews to define BRC and NBRC histories, current and past mental health disorders, and dimensional ratings of PTSD symptomatology. Participants were also administered a number of neuropsychological measures to appraise cognitive functioning. Results A structural equation model (SEM) suggested that BRC and NBRC were not distinct in their prediction of cognitive performance, and there was no evidence that recurrent concussion (blast or nonblast) was directly associated with cognitive performance. BRC was significantly associated with PTSD symptoms (r = .24), PTSD symptoms were significantly associated with cognitive performance in the SEM (r = -.27), and PTSD symptoms significantly mediated the link between BRC and cognitive performance (p = .03). Conclusions These results suggest that concussion history fails to directly contribute to cognitive performance, regardless of mechanism (blast or nonblast) and recurrence. BRC is nonetheless unique in its contribution to PTSD and PTSD-related cognitive deficits. Results support interventions specific to PTSD management in the interest of promoting neuropsychological functioning among war veterans. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Researchers and clinicians have begun using dimensions rather than categories to classify psychopathology with a reliance on personality questionnaires to tap traits that can inform dimensional characterizations. A neglected concern is whether in severe psychopathology questionnaire-based assessments of personality reflect a lifetime propensity toward a diagnosis, as some personality-psychopathology models posit, or reflect the transient effects of current symptoms, as a complication model of personality-psychopathology would suggest. Accurate characterization of psychopathology is necessary to understand etiology and prescribe clinical care. We studied 127 adults with schizophrenia, schizoaffective, or bipolar disorder who completed well-validated measures of personality, current symptomatology, and lifetime psychopathology. We found that normative personality traits were related to current symptoms but unrelated to lifetime symptomatology, whereas the schizotypal trait of cognitive-perceptual distortions predicted lifetime psychosis severity. Questionnaire-based assessments of normative personality are likely affected by current symptom states and may fail to yield a stable characterization of psychopathology.

Objective Cognitive complaints, such as attentional or memory concerns, are commonly reported by veterans diagnosed with posttraumatic stress disorder (PTSD) or a history of mild traumatic brain injury (mTBI). The degree to which those complaints actually map onto measurable cognitive deficits is unclear and is likely complicated by the severity of trauma-related sequelae. In the present study we sought to characterize the degree to which PTSD symptoms and mTBI accounted for the relationship of subjective cognitive complaints to objective cognitive performance, with the goal of facilitating the accurate assessment of trauma-exposed veterans complaining of cognitive decline. Method A sample of 203 U.S. military veterans previously deployed to Iraq and/or Afghanistan were assessed for PTSD severity, history of blast and impact mTBI, objective cognitive function, and subjective cognitive complaints. Separate mediation analyses were conducted to explore the degree that PTSD severity, blast mTBI severity, and impact mTBI severity influenced the association between subjective cognitive complaints and objective cognitive performance. Models reflecting significant mediation were followed by post hoc moderated mediation analyses. Results Subjective cognitive complaints and objective cognitive performance were significantly associated (β = -6.49, SE = 2.85, p = .03), but this relationship was mediated by PTSD severity (β= -2.95, SE = 2.86, p = .30). PTSD mediation was not moderated by either blast or impact mTBI. Conclusion The present results delineate the prominent impact of PTSD symptoms, relative to blast and impact mTBI, on cognition following combat. These findings highlight the importance of assessing for trauma-related psychopathology in those seeking neuropsychological assessment or rehabilitative care for cognitive complaints. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

BACKGROUND: Visual illusions and hallucinations in psychosis likely reflect deviant functions within the hierarchy of visual cortical regions. Recent investigations point to aberrant sensory cortical processes as a source of visual perceptual errors in psychotic disorders like schizophrenia. METHODS: To better understand the basis of errant visual perception in the disorder, we conducted two experiments. First, we combined magneto-encephalography (MEG) and functionally localized magnetic resonance imaging (MRI) data to compute cortical source signals for people with schizophrenia (PSZ) and healthy controls (HCs). Imaging data were acquired while participants detected a simple contour made up of five visual elements that were surrounded by a dense field of similar elements. In our second experiment, we examined event-related potentials (ERPs) recorded during the same contour perception task in PSZ, HCs, as well as people with bipolar affective disorder (PBP) and first-degree biological relatives of PSZ (RelPSZ), which allowed us to examine the diagnostic specificity of perceptual abnormalities. RESULTS: Source signals revealed PSZ to exhibit diminished delta and theta frequency responses in visual cortex. HCs showed theta responses to the contour within visual areas V1 and V3 that were lateralized (contralateral to the visual field where the contour appeared), while PSZ failed to show such lateralization. HCs also had theta responses to the contour that were modulated by the perceptual context created by surrounding stimuli, while this theta modulation was absent in PSZ. Interestingly, PSZ who had stronger contextual modulation of theta in V1 tended to better discern the contours, and PSZ who more strongly modulated theta in V3 reported more unusual perceptual experiences in their daily lives. In the second experiment, contextual modulation of brain responses was absent in the early brain responses (P1 and N1 ERPs prior to 200 msec) for all groups. The P2 ERP response (240 msec), recorded over lateral occipital regions, was significantly modulated by perceptual context, but this modulation was weaker for both PSZ and RelPSZ. These similar aberrations suggest that genetic liability for schizophrenia is associated with diminished suppressive functions in visual cortex involved in visual context processing. CONCLUSIONS: In sum, multimodal imaging and electrophysiological data provide evidence that initial registration of visual stimuli is specifically aberrant in schizophrenia. Diminished effects of perceptual context during contour detection may reflect genetic liability for schizophrenia and is apparent in biological relatives of individuals with this disorder. Additionally, low-frequency oscillations within visual cortex may reflect the pathophysiology of abnormal visual perception in schizophrenia.

BACKGROUND: Individuals with schizophrenia are known to have deficits in social cognition, including theory of mind. Impaired theory of mind has also been reported in first degree biological relatives of individuals with schizophrenia. However, there have been only a few investigations into the neural correlates of theory of mind dysfunction in relatives of individuals with schizophrenia. The current study examined neural activity in individuals with psychosis and first-degree biological relatives during implicit theory of mind, a more automatic and less cognitively demanding component of this social cognitive process. METHODS: Fifty-eight individuals participated in this study; data were collected in the context of a Human Connectome Project study related to human disease focused on psychosis. Participants were 21 individuals with a psychotic disorder, 14 biological first-degree relatives, and 23 controls. Participants underwent fMRI while completing an implicit theory of mind task. In this task, 20 second animations were shown depicting two triangles, with the movement of the triangles corresponding to one of three conditions. In the Theory of Mind condition, the triangles appeared to be interacting with each other and taking each other’s thoughts and feelings into account. In the Physical Interaction condition, the movement of the triangles appeared related (i.e., mirror movement), but the shapes did not appear to be having a social interaction/taking each other’s thoughts and feelings into account. In the Random condition, the shapes’ movements were unrelated to each other. There were six animations presented for each condition across 3 runs, and after viewing each video clip participants selected which type of interaction they believed was going on. fMRI data were analyzed using a canonical preprocessing pipeline in FSL, and first-level GLM analyses modeled neural activity that corresponded to viewing the different types of animations. RESULTS: For the Theory of Mind minus Physical Interaction contrast, there was significantly greater activation in controls compared to both individuals with psychosis and relatives. Specifically, there was one significant cluster of greater activation in controls versus individuals with psychosis (k = 388), and one significant cluster of greater activation in controls versus relatives (k = 287) (corrected cluster significance threshold of p = 0.05). Both of these clusters included right temporoparietal junction (TPJ). There were no areas of activation that were significantly greater in either individuals with psychosis or relatives compared to controls, and there were no significant differences in activation between individuals with psychosis and relatives. DISCUSSION: Results revealed decreased TPJ activation in both individuals with psychosis and relatives compared to controls. TPJ is involved in theory of mind, and abnormalities in TPJ activity have been reported in individuals with schizophrenia during theory of mind. Therefore, these results are consistent with previous literature, and the use of an implicit theory of mind task reduces the concern of confounds related to cognitive deficits. Findings of decreased TPJ activation during implicit theory of mind in relatives suggests that abnormal neural activity during theory of mind may be associated with unexpressed genetic liability for psychosis.

BACKGROUND: Abnormal perceptual experiences are common in people with psychosis and have been linked to greater disease severity and poorer outcomes. While the neural basis of psychosis remains unknown, it has been suggested that an imbalance between excitation and inhibition may lead to neural dysfunction in people with psychotic disorders. It is also unclear to what extent abnormal perceptual functioning occurs across the spectrum of psychotic disorders, or is specific to particular diagnoses (e.g., schizophrenia). METHODS: To examine the link between neural dysfunction and abnormal perception, we performed a series of experiments to measure: 1) visual contrast discrimination behavior, 2) 7 tesla fMRI responses in visual cortex during contrast discrimination, and 3) neurochemical concentrations in visual cortex using 7 tesla MR spectroscopy. Data were acquired from people with psychosis, their unaffected first-degree biological relatives, and healthy control subjects as part of the ongoing Psychosis Human Connectome Project. In our behavioral task performed outside the scanner, subjects were asked to discriminate between two visual grating stimuli, and report which was higher in contrast. Discrimination thresholds, the minimum difference in contrast that could be perceived with 80% accuracy, were measured using a psychophysical adaptive staircase method. Data from 1 subject with psychosis were excluded for poor catch trial performance (< 80% accuracy). RESULTS: Thresholds were significantly higher for subjects with psychosis vs. healthy controls, indicating a reduced sensitivity to visual contrast. Threshold data were fit with a standard model that describes the nonlinear contrast-response function (input vs. output). Preliminary results suggest that the difference in contrast discrimination performance between subjects with psychosis (n = 27) and controls (n = 18) could be described by the model in terms of a multiplicative reduction in visual response magnitude. Preliminary analyses of spectroscopy data revealed no significant differences between subjects with psychosis (n = 22) and controls (n = 25) in the concentrations of glutamate or GABA (scaled to total creatine) in occipital cortex. However, across both groups, higher occipital glutamate concentrations were associated with greater response magnitude values (obtained from modeling the contrast discrimination task data). DISCUSSION: Our results may suggest a role for glutamate levels in occipital cortex in determining individual differences in contrast discrimination performance, as well as in impaired contrast perception among individuals with psychosis.

A quarter of patients with schizophrenia endorse visual hallucinations while two-thirds report subtle perceptual anomalies of visual experience. Yet, little is known about the origin of these visual disturbances and their significance to the disorder. Does schizophrenia represent a unique class of perceptual anomalies or do common mechanisms affect other disorders? Understanding the nature of this defining feature of schizophrenia could help elucidate etiology and address whether visual perceptual phenomena should be considered diagnostic. This symposium will present new findings from four independent laboratories regarding the nature and diagnostic specificity of visual disturbances in schizophrenia. Brian Keane will present results demonstrating visual shape completion deficits in first-episode and chronic schizophrenia patients (d>.8; p

BACKGROUND: The dot pattern expectancy (DPX) task is previously validated for cognitive control deficits in psychotic disorders. Patients with schizophrenia commit more errors as well as show less activation in bilateral prefrontal cortex during proactive control in the DPX task. Recent neural recordings in rhesus macaques indicate that proactive and reactive control processes in the DPX task engaged the same neurons in the prefrontal cortex. However, it is not clear if the overlap between these two mechanisms can be observed in human blood-oxygen-level dependent signals. Further, the role of these dual mechanism regions in the cognitive control deficits of patients with psychotic disorders remains unclear. METHODS: 150 probands with a psychotic disorder, 100 first degree relatives, and 50 healthy controls in the Psychosis Human Connectome Project will complete the DPX task while undergoing 3T functional magnetic resonance imaging scan. Traditional general linear model, as well as a novel multiway method called parallel factor analysis, will be used to examine brain mechanisms involved in proactive as well as reactive control during the DPX task. RESULTS: In a preliminary analysis of 24 probands (38.3 ± 12.8 years, 9 females) and 27 healthy controls (36.2 ± 14.0 years, 11 females), probands showed behavioral deficits in proactive control as compared to healthy controls. Neuroimaging analysis in healthy controls with general linear model showed a cluster in the left inferior frontal gyrus that was involved in both proactive and reactive control. Additionally, overlap in proactive and reactive control was observed in bilateral supramarginal/angular gyrus and right inferior occipital gyrus, although these two mechanisms also involved distinct brain regions. DISCUSSION: Consistent with previous findings, probands showed a specific deficit in proactive control in the DPX task. Proactive and reactive control in healthy controls engaged the same brain regions in the prefrontal cortex, replicating findings in rhesus macaques. Further analyses will reveal the role of the prefrontal cortex as well as other brain regions in the cognitive control deficits in psychotic disorders.

Individuals with schizophrenia exhibit abnormalities in evoked brain responses in oddball paradigms. These could result from (a) insufficient salience-related cortical signaling (P300), (b) insufficient suppression of irrelevant aspects of the auditory environment, or (c) excessive neural noise. We tested whether disruption of ongoing auditory steady-state responses at predetermined frequencies informed which of these issues contribute to auditory stimulus relevance processing abnormalities in schizophrenia. Magnetoencephalography data were collected for 15 schizophrenia and 15 healthy subjects during an auditory oddball paradigm (25% targets; 1-s interstimulus interval). Auditory stimuli (pure tones: 1 kHz standards, 2 kHz targets) were administered during four continuous background (auditory steady-state) stimulation conditions: (1) no stimulation, (2) 24 Hz, (3) 40 Hz, and (4) 88 Hz. The modulation of the auditory steady-state response (aSSR) and the evoked responses to the transient stimuli were quantified and compared across groups. In comparison to healthy participants, the schizophrenia group showed greater disruption of the ongoing aSSR by targets regardless of steady-state frequency, and reduced amplitude of both M100 and M300 event-related field components. During the no-stimulation condition, schizophrenia patients showed accentuation of left hemisphere 40 Hz response to both standard and target stimuli, indicating an effort to enhance local stimulus processing. Together, these findings suggest abnormalities in auditory stimulus relevance processing in schizophrenia patients stem from insufficient amplification of salient stimuli.

Objectives: One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia. Methods: Participants (N=116 controls, 80 patients with schizophrenia) were recruited from four sites. GCA was represented by the first principal component of a large battery of neurocognitive tests. Graph metrics were derived from diffusion-weighted imaging. Results: The global metrics of longer characteristic path length and reduced overall connectivity predicted lower GCA across groups, and group differences were noted for both variables. Measures of clustering, efficiency, and modularity did not differ across groups or predict GCA. Follow-up analyses investigated three topological types of connectivity—connections among high degree “rich club” nodes, “feeder” connections to these rich club nodes, and “local” connections not involving the rich club. Rich club and local connectivity predicted performance across groups. In a subsample (N=101 controls, 56 patients), a genetic measure reflecting mutation load, based on rare copy number deletions, was associated with longer characteristic path length. Conclusions: Results highlight the importance of characteristic path lengths and rich club connectivity for GCA and provide no evidence for group differences in the relationships between graph metrics and GCA. (JINS, 2016, 22, 240–249)

Psychotic disorders have varied clinical presentations, diagnostic stability is poor and other mental disorders often co-occur with the conditions. To improve the clinical and pathophysiological utility of classification systems for psychosis, it is necessary to consider how symptoms may reflect dimensions of psychopathology that extend beyond the boundaries of traditional diagnostic classifications. We examined personality deviation as a means for explaining symptom variation across individuals with serious mental illness. Participants (N = 312) with psychosis, first-degree biological relatives and healthy controls underwent comprehensive clinical evaluations that included symptom ratings and Diagnostic Statistical Manual consensus diagnoses. They completed the Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PID-5), which provides multidimensional assessment of personality disturbances and characterizes psychosis-relevant phenomena, and the Schizotypal Personality Questionnaire (SPQ), a widely accepted measure of schizotypal traits. PID-5 was comparable with SPQ in differentiating between participants with and without psychosis. Greater psychotic symptomatology and higher scores on the SPQ Cognitive-perceptual dimension were associated with higher scores on PID-5 Psychoticism. Facet-level traits showed diverse associations with existing clinical syndromes, suggesting they have utility for quantifying separable symptom dimensions that cut across existing disorders. Yet the patient groups were similar across four of the five PID-5 personality trait domains, indicating shared patterns of personality expression that challenge existing categorical delineations. © 2019 John Wiley & Sons, Ltd.

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30 000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.